VDAC1/Porin

Consists mainly of a membrane-spanning beta-barrel formed by 19 beta-strands (PubMed:18755977, PubMed:18832158). The helical N-terminus folds back into the pore opening and plays a role in voltage-gated channel activity (PubMed:18755977, PubMed:18832158).

Non-selective voltage-gated ion channel that mediates the transport of anions and cations through the mitochondrion outer membrane and plasma membrane (PubMed:10661876, PubMed:11845315, PubMed:18755977, PubMed:30061676, PubMed:8420959). The channel at the outer mitochondrial membrane allows diffusion of small hydrophilic molecules; in the plasma membrane it is involved in cell volume regulation and apoptosis (PubMed:10661876, PubMed:11845315, PubMed:18755977, PubMed:8420959). It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV (PubMed:10661876, PubMed:18755977, PubMed:8420959). The open state has a weak anion selectivity whereas the closed state is cation-selective (PubMed:18755977, PubMed:8420959). Binds various signaling molecules, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterols cholesterol and oxysterol (PubMed:18755977, PubMed:31015432). In depolarized mitochondria, acts downstream of PRKN and PINK1 to promote mitophagy or prevent apoptosis; polyubiquitination by PRKN promotes mitophagy, while monoubiquitination by PRKN decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:32047033). May participate in the formation of the permeability transition pore complex (PTPC) responsible for the release of mitochondrial products that triggers apoptosis (PubMed:15033708, PubMed:25296756). May mediate ATP export from cells (PubMed:30061676). Part of a complex composed of HSPA9, ITPR1 and VDAC1 that regulates mitochondrial calcium-dependent apoptosis by facilitating calcium transport from the ER lumen to the mitochondria intermembrane space thus providing calcium for the downstream calcium channel MCU that directly releases it into mitochondria matrix (By similarity). Mediates cytochrome c efflux (PubMed:20230784).

Catalyzes the scrambling of phospholipids across the outer mitochondrial membrane; the mechanism is unrelated to channel activity and is capable of translocating both anionic and zwitterionic phospholipids.

Phosphorylation at Ser-193 by NEK1 promotes the closed conformational state preventing excessive mitochondrial membrane permeability and subsequent apoptotic cell death after injury (PubMed:20230784). Phosphorylation by the AKT-GSK3B axis stabilizes the protein probably by preventing ubiquitin-mediated proteasomal degradation.

Ubiquitinated (PubMed:25621951, PubMed:32047033). Undergoes monoubiquitination and polyubiquitination by PRKN; monoubiquitination at Lys-274 inhibits apoptosis, whereas polyubiquitination leads to its degradation and promotes mitophagy (PubMed:25621951, PubMed:32047033). Deubiquitinated by USP30 (PubMed:25621951).

Belongs to the eukaryotic mitochondrial porin family.

Expressed in erythrocytes (at protein level) (PubMed:27641616). Expressed in heart, liver and skeletal muscle (PubMed:8420959).

• Mitochondrion outer membrane
• Multi-pass membrane protein
• Cell membrane
• Multi-pass membrane protein
• Membrane raft
• Multi-pass membrane protein
• Found in a complex with HSPA9 and VDAC1 at the endoplasmic reticulum-mitochondria contact sites.

VDAC, VDAC1, Non-selective voltage-gated ion channel VDAC1, Outer mitochondrial membrane protein porin 1, Plasmalemmal porin, Porin 31HL, Porin 31HM, Voltage-dependent anion-selective channel protein 1, VDAC-1, hVDAC1

• entrezGene:7416
• omim:604492
• swissprot:P21796

Proteins

Neuroscience

• Immunology & Infectious Disease

30773Da